Q16602 (CALRL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcitonin gene-related peptide type 1 receptor
Short name=CGRP type 1 receptor

Alternative name(s):
Calcitonin receptor-like receptor

Gene names

Name:	CALCRL
Synonyms:	CGRPR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	461 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 By similarity. Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Ref.8
Subunit structure	Heterodimer of CALCRL and RAMP3 By similarity. Heterodimer of CALCRL and RAMP1 or CALCRL and RAMP2. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Predominantly expressed in the lung and heart.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.
Sequence caution	The sequence BAF84319.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Traceable author statement Ref.2. Source: ProtInc adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara angiogenesis Inferred from direct assay PubMed 20596610. Source: UniProtKB cAMP biosynthetic process Inferred from direct assay PubMed 20074556. Source: UniProtKB calcium ion transport Inferred from direct assay PubMed 10882736. Source: UniProtKB cellular response to sucrose stimulus Inferred from direct assay PubMed 10882736. Source: UniProtKB heart development Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of cAMP biosynthetic process Inferred from direct assay PubMed 10882736PubMed 9620797. Source: UniProtKB positive regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara receptor internalization Inferred from direct assay PubMed 20074556. Source: UniProtKB regulation of muscle contraction Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum Inferred from direct assay PubMed 10882736. Source: UniProtKB endosome Inferred from direct assay PubMed 10882736. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc lysosome Inferred from direct assay PubMed 10882736. Source: UniProtKB
Molecular_function	adrenomedullin receptor activity Inferred from direct assay Ref.8. Source: UniProtKB calcitonin gene-related polypeptide receptor activity Inferred from electronic annotation. Source: Compara calcitonin receptor activity Inferred from electronic annotation. Source: Compara protein transporter activity Inferred from direct assay PubMed 9620797. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.6

Chain

23 – 461

439

Calcitonin gene-related peptide type 1 receptor

PRO_0000012811

Regions

Topological domain

23 – 146

124

Extracellular Potential

Transmembrane

147 – 166

20

Helical; Name=1; Potential

Topological domain

167 – 173

7

Cytoplasmic Potential

Transmembrane

174 – 193

20

Helical; Name=2; Potential

Topological domain

194 – 213

20

Extracellular Potential

Transmembrane

214 – 236

23

Helical; Name=3; Potential

Topological domain

237 – 253

17

Cytoplasmic Potential

Transmembrane

254 – 273

20

Helical; Name=4; Potential

Topological domain

274 – 289

16

Extracellular Potential

Transmembrane

290 – 313

24

Helical; Name=5; Potential

Topological domain

314 – 336

23

Cytoplasmic Potential

Transmembrane

337 – 354

18

Helical; Name=6; Potential

Topological domain

355 – 366

12

Extracellular Potential

Transmembrane

367 – 388

22

Helical; Name=7; Potential

Topological domain

389 – 461

73

Cytoplasmic Potential

Amino acid modifications

Glycosylation

66

1

N-linked (GlcNAc...) Potential

Glycosylation

118

1

N-linked (GlcNAc...) Potential

Glycosylation

123

1

N-linked (GlcNAc...) Potential

Disulfide bond

48 ↔ 74

Ref.7 Ref.8

Disulfide bond

65 ↔ 105

Ref.7 Ref.8

Disulfide bond

88 ↔ 127

Ref.7 Ref.8

Natural variations

Natural variant

8

1

N → Y. Ref.4
Corresponds to variant rs698577 [ dbSNP | Ensembl ].

VAR_054822

Natural variant

16

1

F → L.
Corresponds to variant rs13391909 [ dbSNP | Ensembl ].

VAR_049453

Natural variant

274

1

R → I.
Corresponds to variant rs34010553 [ dbSNP | Ensembl ].

VAR_049454

Experimental info

Mutagenesis

72

1

W → A: Strongly reduced affinity for adrenomedullin. Ref.8

Mutagenesis

92

1

F → A: Strongly reduced affinity for adrenomedullin. Ref.8

Mutagenesis

121

1

W → A: Strongly reduced affinity for adrenomedullin. Ref.8

Sequence conflict

144

1

L → Q in BAF84319. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

461

Helix Strand Turn

Details...

Helix

33 – 52

20

Beta strand

63 – 65

3

Beta strand

83 – 87

5

Beta strand

90 – 92

3

Beta strand

99 – 105

7

Turn

115 – 117

3

Helix

125 – 127

3

Helix

129 – 131

3

Sequences

	Sequence		Length	Mass (Da)
	Q16602 [UniParc]. Last modified April 14, 2009. Version 2. Checksum: AF98E55E5454767C	FASTA	461	52,929
	10 20 30 40 50 60 MEKKCTLNFL VLLPFFMILV TAELEESPED SIQLGVTRNK IMTAQYECYQ KIMQDPIQQA 70 80 90 100 110 120 EGVYCNRTWD GWLCWNDVAA GTESMQLCPD YFQDFDPSEK VTKICDQDGN WFRHPASNRT 130 140 150 160 170 180 WTNYTQCNVN THEKVKTALN LFYLTIIGHG LSIASLLISL GIFFYFKSLS CQRITLHKNL 190 200 210 220 230 240 FFSFVCNSVV TIIHLTAVAN NQALVATNPV SCKVSQFIHL YLMGCNYFWM LCEGIYLHTL 250 260 270 280 290 300 IVVAVFAEKQ HLMWYYFLGW GFPLIPACIH AIARSLYYND NCWISSDTHL LYIIHGPICA 310 320 330 340 350 360 ALLVNLFFLL NIVRVLITKL KVTHQAESNL YMKAVRATLI LVPLLGIEFV LIPWRPEGKI 370 380 390 400 410 420 AEEVYDYIMH ILMHFQGLLV STIFCFFNGE VQAILRRNWN QYKIQFGNSF SNSEALRSAS 430 440 450 460 YTVSTISDGP GYSHDCPSEH LNGKSIHDIE NVLLKPENLY N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A cDNA encoding the calcitonin gene-related peptide type 1 receptor." Aiyar N., Rand K., Elshourbagy N.A., Zeng Z., Adamou J.E., Bergsma D.J., Li Y. J. Biol. Chem. 271:11325-11329(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"A human orphan calcitonin receptor-like structure." Fluehmann B., Muff R., Hunziker W., Fischer J.A., Born W. Biochem. Biophys. Res. Commun. 206:341-347(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cerebellum.
[3]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-8. Tissue: Placenta and Trachea.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-37.
[7]	"Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism." ter Haar E., Koth C.M., Abdul-Manan N., Swenson L., Coll J.T., Lippke J.A., Lepre C.A., Garcia-Guzman M., Moore J.M. Structure 18:1083-1093(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 23-133 IN COMPLEX WITH RAMP1 AND ANTAGONIST, SUBUNIT, DISULFIDE BONDS.
[8]	"Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding." Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Okuda K., Sakamoto K., Shirouzu M., Shindo T., Yokoyama S. Protein Sci. 21:199-210(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 23-136 IN COMPLEX WITH RAMP2, FUNCTION, MUTAGENESIS OF TRP-72; PHE-92 AND TRP-121, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L76380 mRNA. Translation: AAC41994.1.
U17473 mRNA. Translation: AAA62158.1.
AY389506 mRNA. Translation: AAQ91332.1.
AK291630 mRNA. Translation: BAF84319.1. Different initiation.
AK292998 mRNA. Translation: BAF85687.1.
AC007319 Genomic DNA. Translation: AAY14806.1.
AC074020 Genomic DNA. Translation: AAY14996.1.

IPI

IPI00873582.

PIR

JC2477.

RefSeq

NP_001258680.1. NM_001271751.1.
NP_005786.1. NM_005795.5.

UniGene

Hs.470882.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3AQF	X-ray	2.60	B	23-136	[»]
3N7P	X-ray	2.80	A/B/C/J	23-133	[»]
3N7R	X-ray	2.90	A/B	23-133	[»]
3N7S	X-ray	2.10	A/B	23-133	[»]

ProteinModelPortal

Q16602.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37674N.

IntAct

Q16602. 2 interactions.

STRING

9606.ENSP00000376177.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

Q16602.

Polymorphism databases

DMDM

226693507.

Proteomic databases

PaxDb

Q16602.

PRIDE

Q16602.

Protocols and materials databases

DNASU

10203.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000392370; ENSP00000376177; ENSG00000064989.
ENST00000409998; ENSP00000386972; ENSG00000064989.
ENST00000410068; ENSP00000387190; ENSG00000064989.

GeneID

10203.

KEGG

hsa:10203.

UCSC

uc010frt.3. human.

Organism-specific databases

CTD

10203.

GeneCards

GC02M188171.

HGNC

HGNC:16709. CALCRL.

HPA

HPA008070.

MIM

114190. gene.

neXtProt

NX_Q16602.

PharmGKB

PA26033.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG255868.

HOVERGEN

HBG102129.

InParanoid

Q16602.

KO

K04577.

OMA

NYTQCNV.

OrthoDB

EOG4WSW9H.

PhylomeDB

Q16602.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q16602.

Bgee

Q16602.

CleanEx

HS_CALCRL.

Genevestigator

Q16602.

GermOnline

ENSG00000064989. Homo sapiens.

Family and domain databases

InterPro

IPR003287. GCPR_2_calcitonin_rcpt_fam.
IPR017981. GPCR_2-like.
IPR003289. GPCR_2_CGRP1_rcpt.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]

PANTHER

PTHR12011:SF67. PTHR12011:SF67. 1 hit.

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR01351. CGRPRECEPTOR.
PR01350. CTRFAMILY.
PR00249. GPCRSECRETIN.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

PROSITE

PS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16602.

ChEMBL

CHEMBL3798.

EvolutionaryTrace

Q16602.

GenomeRNAi

10203.

NextBio

38620.

SOURCE

Search...

Entry information

Entry name

CALRL_HUMAN

Accession

Primary (citable) accession number: Q16602
Secondary accession number(s): A8K6G5 , A8KAD3, Q53S02, Q53TS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 14, 2009
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.